Molding Minds: The Roman Use of the Cuirassed Statue in Defining Empire

Though a Roman emperor possessed a wide variety of media on which he could address his subjects- coins, arches, decrees- one of the most presently understudied is that of the cuirassed statue. In this artistic genre, the emperor was portrayed in the guise of a triumphant general while performing an adlocutio or simply holding a spear or globe to signify imperial global hegemony. Though the gesture of the ruler is certainly important, in the present study I am examining the function of the face of the breastplate as it concerns imperial propaganda. On this stone canvass the artist carved messages that enabled an emperor to advertise his latest military victory while subtly directing the thoughts of his subjects in regards to how they viewed both their own unique place within the empire and the barbaric "others" outside of it. In particular, the image of the demoralized and defeated barbarian was an especially popular and potent device utilized by many emperors to commemorate a specific victory. Through the agency of the cuirass, for example, citizens in Gaul learned of the subjugation of Judea; a land that was far removed geographically and likely not a part of their conception of the world; that is, until the emperor brought both knowledge of his victory and images of this alien people to their collective psyches. Thus, the narrative on the cuirass shaped how the Gauls viewed the emperor, the empire, and the distant peoples who challenged Rome. By examining important works within the genre and with a keen eye towards historical contexts and modern theoretical approaches, I hope to come to a fuller understanding of the ways in which a ruler strived to construct the opinions and memories of his subjects.No embarg

Phase I Study of Zotiraciclib in Combination with Temozolomide for Patients with Recurrent High-grade Astrocytomas

PURPOSE: To investigate the toxicity profile and establish an optimal dosing schedule of zotiraciclib with temozolomide (TMZ) in patients with recurrent high-grade astrocytoma. EXPERIMENTAL DESIGN: This two-stage phase 1 trial determined the maximum tolerated dose (MTD) of zotiraciclib combined with either dose-dense (Arm1) or metronomic (Arm2) TMZ using a Bayesian Optimal Interval design; then a randomized cohort-expansion compared the progression-free survival rate at 4 month (PFS4) of the two arms for an efficient determination of a TMZ schedule to combine with zotiraciclib at MTD. Pharmacokinetics (PK) and pharmacogenomic (PG) profiling were included. Patient-reported outcome was evaluated by longitudinal symptom burden. RESULTS: Fifty-three patients were enrolled. Dose-limiting toxicities were neutropenia, diarrhea, elevated liver enzymes, and fatigue. MTD of zotiraciclib was 250mg in both arms and thus selected for the cohort expansion. Dose-dense TMZ plus zotiraciclib (PSF4 40%) compared favorably with metronomic TMZ (PFS4 25%). Symptom burden worsened at Cycle 2 but stabilized by Cycle 4 in both arms. A significant decrease in absolute neutrophil count and neutrophil reactive oxygen species production occurred 12–24 hours after an oral dose of zotiraciclib but both recovered by 72 hours. PK/PG analyses revealed that the CYP1A2_5347T>C (rs2470890) polymorphism was associated with higher AUC(inf) value. CONCLUSIONS: Zotiraciclib combined with TMZ is safe in patients with recurrent high-grade astrocytomas. Zotiraciclib-induced neutropenia can be profound but mostly transient, warranting close monitoring rather than treatment discontinuation. Once validated, polymorphisms predicting drug metabolism may allow personalized dosing of zotiraciclib

Phase I Study of Zotiraciclib in Combination with Temozolomide for Patients with Recurrent High-grade Astrocytomas

PurposeTo investigate the toxicity profile and establish an optimal dosing schedule of zotiraciclib with temozolomide in patients with recurrent high-grade astrocytoma.Patients and methodsThis two-stage phase I trial determined the MTD of zotiraciclib combined with either dose-dense (Arm1) or metronomic (Arm2) temozolomide using a Bayesian Optimal Interval design; then a randomized cohort expansion compared the progression-free survival rate at 4 months (PFS4) of the two arms for an efficient determination of a temozolomide schedule to combine with zotiraciclib at MTD. Pharmacokinetic and pharmacogenomic profiling were included. Patient-reported outcome was evaluated by longitudinal symptom burden.ResultsFifty-three patients were enrolled. Dose-limiting toxicities were neutropenia, diarrhea, elevated liver enzymes, and fatigue. MTD of zotiraciclib was 250 mg in both arms and thus selected for the cohort expansion. Dose-dense temozolomide plus zotiraciclib (PSF4 40%) compared favorably with metronomic temozolomide (PFS4 25%). Symptom burden worsened at cycle 2 but stabilized by cycle 4 in both arms. A significant decrease in absolute neutrophil count and neutrophil reactive oxygen species production occurred 12-24 hours after an oral dose of zotiraciclib but both recovered by 72 hours. Pharmacokinetic/pharmacogenomic analyses revealed that the CYP1A2_5347T>C (rs2470890) polymorphism was associated with higher AUCinf value.ConclusionsZotiraciclib combined with temozolomide is safe in patients with recurrent high-grade astrocytomas. Zotiraciclib-induced neutropenia can be profound but mostly transient, warranting close monitoring rather than treatment discontinuation. Once validated, polymorphisms predicting drug metabolism may allow personalized dosing of zotiraciclib